Duration of Chemotherapy-Induced Nausea and Vomiting (CINV) as a Predictor of Recurrent CINV in Later Cycles.

BACKGROUND: The relationship between CINV duration and recurrence in subsequent cycles is largely unstudied. Our objective was to determine if patients experiencing CINV in their first cycle of chemotherapy (C1) would face increased risk of CINV in later cycles and whether the duration of the CINV would predict increased risk of recurrence. PATIENTS AND METHODS: Using data from a previously reported phase III trial, we assessed patients' recurrence of breakthrough CINV after antiemetic prophylaxis for anthracycline+cyclophosphamide (AC) for breast cancer, comparing C1 short CINV vs. extended CINV as a secondary analysis. Complete response (CR) and CINV duration were primary and secondary endpoints, respectively. CR was considered prophylaxis success; lack of CR was considered treatment failure (TF). RESULTS: Among 402 female patients, 99 (24.6%) had TF in C1 (TF1). The remaining 303 patients (CR1) had ≥93% CR rates in each subsequent cycle, while the 99 patients with TF1 had TF rates of 49.8% for cycles 2-4 (P < .001). The 51 patients with extended TF (≥3 days) in C1 had recurrent TF in 73/105 later cycles (69.5%, P < .001), while the 48 patients with short TF (1-2 days) in C1 had recurrent TF in 33/108 later cycles (30.6%). The relative risk of recurrence after C1 extended TF was 2.28 (CI 1.67-3.11; P < .001) compared to short TF. CONCLUSIONS: Prophylaxis success in C1 led to >90% repeat success across cycles of AC-based chemotherapy. For patients with breakthrough CINV, extended duration strongly predicted recurrent CINV. The duration of CINV should be closely monitored, and augmenting antiemetic prophylaxis considered for future cycles when extended CINV occurs.

2023 updated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting.

PURPOSE: This review is an update of the MASCC/ESMO 2015 recommendations for the prophylaxis of acute and delayed nausea and vomiting induced by multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting. METHODS: A systematic literature search was conducted using PubMed from June 1, 2015, through February 1, 2023. RESULTS: We identified 56 references (16 were duplications or invalid), leaving 40 manuscripts for this search. The panel classified level I evidence (three manuscripts) and level II evidence (14 manuscripts). High-dose chemotherapy and stem cell transplant were discussed in four of these manuscripts, and multiple-day chemotherapy treatment in 15. Some manuscripts covered both topics. Additionally, a search for breakthrough nausea and vomiting resulted in 12 "hits." No new relevant studies were identified. CONCLUSIONS: The recommendations for patients receiving high-dose chemotherapy with stem cell transplants and patients undergoing multiple-day cisplatin were updated. For patients receiving high-dose chemotherapy for stem cell transplant, a combination of a 5-HT3 receptor antagonist with dexamethasone and aprepitant is recommended. Olanzapine could be considered part of the antiemetic regimen. Patients receiving multiple-day cisplatin should receive a 5-HT3 receptor antagonist plus dexamethasone plus aprepitant plus olanzapine. For patients experiencing breakthrough nausea and vomiting, the available evidence suggests using a single dose of olanzapine daily for 3 days.

Prevalence and predictors of long-delayed (> 120 h) chemotherapy-induced nausea and vomiting (CINV)-a systematic review and individual patient data meta-analysis.

INTRODUCTION: Although there have been reports of chemotherapy-induced nausea and vomiting (CINV) beyond 120 h, its overall prevalence has not been systematically examined. The aim of this review and meta-analysis was to report on the prevalence of this long-delayed CINV. METHODS: This review was registered on PROSPERO (CRD42022346963). PubMed (Medline), Embase, and Cochrane Central were searched from inception until August 2022. Articles were included if they reported on CINV > 120 h after initiation of the chemotherapy regimen and patients received a single-agent highly emetogenic (HEC) or moderately emetogenic (MEC) antineoplastic agent for 1 day alone or in combination with low/minimal emetogenic chemotherapy. For all eligible articles, individual study authors were contacted and requested to provide individual patient-level data of demographics, emetogenicity of chemotherapy regimens, and daily incidence of nausea and vomiting. Forward stepwise logistic regression identified predictors for the incident day's CINV based on prior day's CINV episodes, controlling for patient demographics, and stratified by regimen emetogenicity. RESULTS: A total of 2048 patients from 2 studies were included in this individual patient data meta-analysis: 1333 patients (65%) received HEC and 715 (35%) received MEC. Among those receiving HEC, 325 (24%) experienced acute, 652 (49%) delayed, and 393 (31%) long-delayed nausea; 107 (8%) experienced acute, 179 (14%) delayed, and 79 (6%) long-delayed vomiting. Among those receiving MEC, 48 (7%) experienced acute, 272 (38%) delayed, and 167 (24%) long-delayed nausea; 12 (2%) experienced acute, 97 (14%) delayed, and 42 (6%) long-delayed vomiting. Nausea in the long-delayed phase was as severe as in the delayed phase. Patients experiencing nausea and vomiting on days 4 and 5 were at significant risk of experiencing long-delayed CINV. CONCLUSION: While not as prevalent as delayed nausea and vomiting, long-delayed CINV affects a significant proportion of patients and severity is similar. Patients with delayed CINV, specifically on days 4-5, are at risk of experiencing long-delayed CINV.

2023 updated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following high-emetic-risk antineoplastic agents.

PURPOSE: This systematic review updates the MASCC/ESMO recommendations for high-emetic-risk chemotherapy (HEC) published in 2016-2017. HEC still includes cisplatin, carmustine, dacarbazine, mechlorethamine, streptozocin, and cyclophosphamide in doses of > 1500 mg/m2 and the combination of cyclophosphamide and an anthracycline (AC) in women with breast cancer. METHODS: A systematic review report following the PRISMA guidelines of the literature from January 1, 2015, until February 1, 2023, was performed. PubMed (Ovid), Scopus (Google), and the Cochrane Database of Systematic Reviews were searched. The literature search was limited to randomized controlled trials, systematic reviews, and meta-analyses. RESULTS: Forty-six new references were determined to be relevant. The main topics identified were (1) steroid-sparing regimens, (2) olanzapine-containing regimens, and (3) other issues such as comparisons of antiemetics of the same drug class, intravenous NK1 receptor antagonists, and potentially new antiemetics. Five updated recommendations are presented. CONCLUSION: There is no need to prescribe steroids (dexamethasone) beyond day 1 after AC HEC, whereas a 4-day regimen is recommended in non-AC HEC. Olanzapine is now recommended as a fixed part of a four-drug prophylactic antiemetic regimen in both non-AC and AC HEC. No major differences between 5-HT3 receptor antagonists or between NK1 receptor antagonists were identified. No new antiemetic agents qualified for inclusion in the updated recommendations.

2023 updated MASCC/ESMO Consensus recommendations: Prevention of nausea and vomiting following moderately emetic risk antineoplastic agents.

PURPOSE: Review the literature to update the MASCC guidelines from 2015 for controlling nausea and vomiting with systemic cancer treatment of moderate emetic potential. METHODS: A systematic literature review was completed using Medline, Embase, and Scopus databases. The literature search was done from June 2015 to January 2023 of the management of antiemetic prophylaxis for anticancer therapy of moderate emetic potential. RESULTS: Of 342 papers identified, 19 were relevant to update recommendations about managing antiemetic prophylaxis for systemic cancer treatment regimens of moderate emetic potential. Important practice changing updates include the use of emetic prophylaxis based on a triple combination of neurokinin (NK)1 receptor antagonist, 5-HT3 receptor antagonist, and steroids for patients undergoing carboplatin (AUC ≥ 5) and women < 50 years of age receiving oxaliplatin-based treatment. A double combination of 5-HT3 receptor antagonist and steroids remains the recommended prophylaxis for other MEC. Based on the data in the literature, it is recommended that the administration of steroids should be limited to day 1 in moderately emetogenic chemotherapy regimens, due to the demonstration of non-inferiority between the different regimens. More data is needed on the emetogenicity of new agents at moderate emetogenic risk. Of particular interest would be antiemetic studies with the agents sacituzumab-govitecan and trastuzumab-deruxtecan. Experience to date with these agents indicate an emetogenic potential comparable to carboplatin > AUC 5. Future studies should systematically include patient-related risk assessment in order to define the risk of emesis with MEC beyond the emetogenicity of the chemotherapy and improve the guidelines for new drugs. CONCLUSION: This antiemetic MASCC-ESMO guideline update includes new recommendations considering individual risk factors and the optimization of supportive anti-emetic treatments.

The prevalence, distribution and impact of peripheral neuropathy among Danish patients with cancer - a population-based cross-sectional study.

BACKGROUND: Prevalence of peripheral neuropathy (PN) has been studied in patients undergoing treatment with taxanes, platinums and vinca alkaloids. The prevalence is unknown in the general oncological cancer population, characterized by advanced age, comorbidities and heterogeneous treatments. MATERIAL AND METHODS: A cross-sectional survey was administered to all adult patients, attending outpatient services at three Danish departments of oncology. The survey contained the EORTC-CIPN20, the EORTC-QLQ-C30, the GAD7 and PHQ9 questionnaires. A high PN symptom score was defined as a summary score ≥30 points on the CIPN20. P-values were adjusted for multiple testing. RESULTS: With an overall response rate of 83% (2839 patients), prevalence of PN was 17% overall, varying from 6 to 33% between diagnosis groups.A high score was more common among females (19 vs. 14%, p = .008), smokers (21 vs. 15%, p = .04), patients living alone (21 vs. 15%, p = .002) and patients using cannabis (29 vs. 15%, p < .001), as well as patients suffering from diabetes (26 vs. 16%, p < .001), cardiac heart disease (27 vs. 16%, p < .001), arthritis (32 vs. 15%, p < .001) or chronic obstructive pulmonary disease (25 vs. 16%, p = .01). High score patients were also older (69ys vs 67ys, p = .048) and more likely experiencing polypharmacy (OR = 3.38 [95% CI, 2.64;4.35]).Patients with a high CIPN20 symptom score scored worse on all EORTC QLQ-C30 function and symptom scales. The mean adjusted C30 SumScore difference was -18.66 ([95% CI, -20.31; -17.02], p < .001). CONCLUSION: Symptoms of PN are experienced widely across cancer groups in the oncology setting. PN symptoms were associated with clinically relevant worse health-related quality of life and with patient-related factors as living alone, various comorbidities, polypharmacy, and cannabis use.

Nonepithelial ovarian cancer - the current clinical practice in the Nordic countries. Survey from the surgical subcommittee of the Nordic society of gynecological oncology (NSGO).

BACKGROUND: Nonepithelial ovarian cancer (NEOC) represents a wide variety of rare tumors. They are often diagnosed at an early stage and have a good prognosis compared to epithelial ovarian cancer. In the Nordic countries, the total annual number of patients diagnosed with ovarian cancer, Fallopian tube cancer or primary peritoneal carcinoma (hereafter ovarian cancer) was 2281 in 2014-2018, of which 3-10% were NEOC. International guidelines for diagnosis, treatment and follow-up have been developed. We present the results of a survey, aiming at clarifying current clinical practice in the Nordic countries. MATERIAL AND METHODS: Between 09.2020 and 02.2021 a 33-question electronic survey was distributed to 22 hospitals in Finland, Sweden, Norway, Iceland and Denmark via the Nordic Society of Gynecological Oncology (NSGO) National Representatives. Data were collected in a secure web-based software platform. The questionnaire focused on demographics, diagnosis, treatment and follow-up programs. RESULTS: Twenty-one (95,4%) centers completed the survey. A total of 155 annual new NEOC cases treated in the Nordic countries were reported, corresponding to approximately 7% of all ovarian cancer cases. Most centers measured some or all of the recommended biomarkers routinely. Vaginal ultrasound and computed tomography (CT) were the preferred imaging modalities. The majority of centers conducted multidisciplinary team (MDT) meetings. The primary reported treatment was surgery. In 65% of centers, lymph node dissection was only performed in cases with suspicious lymph nodes. Surveillance was usually offered > four years. DISCUSSION: Despite, the presence of clinical European guidelines, variation in the current clinical practice amongst participating centers adhering to national guidelines was observed. Prospective clinical national research programs are sparse, and an enhanced cooperation in the Nordic countries toward development of a Nordic guideline and database is highly warranted and a prerequisite for future research, preferably in cooperation with the larger international groups.

Cannabis use among Danish patients with cancer: a cross-sectional survey of sociodemographic traits, quality of life, and patient experiences.

PURPOSE: Patients with cancer are using cannabis for self-treatment. The reasons, experienced effects, and prevalence of use are unknown in the European general oncological population. METHODS: Adult patients with cancer attending outpatient oncology clinics were invited to participate in a cross-sectional survey. The questionnaire consisted of sociodemographic questions, validated scales on quality of life, neuropathy, anxiety and depression as well as questions regarding use of cannabis. RESULTS: The overall response rate was 83% (2839 patients) and 13% of patients were using or had used cannabis during their treatment. Rate of use was higher in smokers (19% vs 11%, p adjusted 0.002), in patients in active cancer treatment (14% vs 10%, p adjusted = 0.02), and in patients with depression (19% vs 11%, adjusted p = 0.002). Cannabis use was also correlated with lower quality of life (EORTC C30 SumScore mean diff. = - 7.61, 95% CI = [- 9.69; - 5.53]). In total, 77% of users experienced at least one positive effect of cannabis, 18% experienced no effect, and 5% experienced other effects. At least one side effect was experienced by 33% of users. Management of pain and nausea were the primary reasons for initiating cannabis use (39% for both). Less nausea and better sleep were the most common effects experienced (26% for both). Oils for oral use were the most common route of administration (88%). CONCLUSION: Cannabis use among patients with cancer is prevalent and correlated with worse quality of life. Patients report using cannabis for symptom management and many experience relief of their symptoms. However, one third of patients experienced side effects.

Oral cannabidiol for prevention of acute and transient chemotherapy-induced peripheral neuropathy.

PURPOSE: To assess the safety, dosing, and preventive effects of cannabidiol (CBD) on chemotherapy-induced peripheral neuropathy (CIPN) in patients receiving oxaliplatin- or paclitaxel-based chemotherapy. METHODS: Patients with cancer scheduled to undergo treatment with carboplatin and paclitaxel (Carbo-Tax) or capecitabine and oxaliplatin (CAPOX) received 150 mg CBD oil twice daily (300 mg/daily) for 8 days beginning 1 day before initiation of chemotherapy. Ten CIPN-specific patient-reported outcome (PRO) measures were captured at baseline and each day after the first cycle of chemotherapy for 8 days. Multi-frequency vibrometry (MF-V) was captured at baseline and day 4 ± 1 after initiation of chemotherapy. Controls were obtained from a similar patient cohort that did not receive CBD. Adverse events were captured using the CTCAE ver. 4.03. RESULTS: From March to December 2021, 54 patients were recruited. CBD-treated patients were significantly older (p = 0.013/0.037, CAPOX/Carbo-Tax) compared to controls. Patients receiving CBD and CAPOX or Carbo-Tax showed significantly lower (better) change in Z-scores in high-frequency MF-V (125 and 250 Hz) compared to controls. This difference was most pronounced for patients receiving Carbo-Tax (- 1.76, CI-95 = [- 2.52; - 1.02] at 250 Hz). CAPOX patients treated with CBD had significantly lower peak baseline-adjusted difference in three PRO items on cold sensitivity to touch, discomfort swallowing cold liquids, and throat discomfort (- 2.08, - 2.06, and - 1.81, CI-95 = [- 3.89; - 0.12], NRS 0-10). No significant differences in PRO items were found for patients receiving Carbo-Tax. Possible side effects included stomach pain (grades 1-2) for patients receiving CAPOX. CONCLUSION: CBD attenuated early symptoms of CIPN with no major safety concerns. Long-term follow-up is ongoing. Results should be confirmed in a larger, randomized study. TRIAL REGISTRATION NUMBER: NCT 04,167,319 (U.S National Library of Medicine; ClinicalTrials.gov). Date of registration: November 18, 2019.

Teaching supportive care: what is the core curriculum?

PURPOSE OF REVIEW: Cancer treatment options have developed rapidly in the past years. Targeted- and immune therapy have resulted in additional supportive care needs. This review describes a teaching program in supportive care. RECENT FINDINGS: Supportive care begins at the time of cancer diagnosis and continues until the patient has died or is cured and late toxicities and other survivorship issues have been properly addressed. Supportive care is divided into four phases. In the curative phase, competences regarding prevention and management of acute treatment and subacute treatment side effects are important. In the survivorship phase, competences related to late toxicity and chronic toxicity are warranted. In the palliative phase, focus will be on competences concerning cancer complications, and specific end-of-life competences are needed as well. Obviously some competences are needed in all phases, for example, communication skills. SUMMARY: Competences concerning symptoms and complications are summarized for each phase in table format. General competences are listed in the text body of the manuscript. Regular update and implementation is crucial. The future cancer population will consist of a higher number of older cancer patients and survivors. This should reflect curriculum updates as should the increasing possibilities for multigene sequencing enabling personal medicine (including supportive care) to a larger extent than today.

Differential effects of colorectal cancer screening across sociodemographic groups in Denmark: a register-based study.

INTRODUCTION: Colorectal cancer (CRC) does not affect different sociodemographic groups uniformly. CRC screening programmes could seek to reduce this inequality; however, the screening programmes themselves might be subject to differential participation across sociodemographic groups. This study investigates the sociodemographic inequality at all steps in Denmark's nationwide CRC screening programme: screening participation, faecal immunochemical test (FIT) results, colonoscopy compliance, CRC diagnosis, and cancer stage. MATERIAL AND METHODS: This cohort study includes all first-time invitees from the beginning of the Danish population-based CRC screening programme from 1 March 2014 to 31 December 2017. RESULTS: Sixty-four percent of the invitees participated in the screening programme, and of those 7% were FIT-positive. After being invited to further diagnostic procedures, 90% responded to the invitation, and among those 5% were CRC-positive. Among those diagnosed with CRC, 9% were stage IV. Through multivariable analyses, we identified sociodemographic inequalities in all steps of the screening programme from returning a stool sample to being diagnosed with CRC. Specifically, we identified inequalities across sex, age, migration status, relationship status, the screening status of one's partner, education, income, and use of health services. Women were more likely to participate compared to men (RR = 1.13; 95% CI: 1.12-1.13), but had a lower risk of a positive FIT result (RR = 0.67; 95% CI: 0.66-0.68) and of a CRC diagnosis (RR = 0.88; 95% CI: 0.82-0.93) compared to men. The likelihood of participating as well as the risk of positive FIT results and CRC diagnosis increased with age. CONCLUSION: All steps of the screening programme were subject to sociodemographic inequalities. Interventions are needed to target groups identified as having lower uptake as well as high-risk of being FIT- and/or CRC-positive. These groups include males, individuals aged 60+ years and individuals who do not visit their GP regularly.

Cost-effectiveness analysis of olanzapine-containing antiemetic therapy for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in highly emetogenic chemotherapy (HEC) patients.

PURPOSE: Olanzapine-containing regimens have been reported to be effective in preventing CINV following highly emetogenic chemotherapy (HEC), but it is unsure whether it is cost-effective. There has been no cost-effectiveness analysis conducted for olanzapine using costs from the USA. The aim of this study is to determine whether olanzapine-containing antiemetic regimens are cost-effective in patients receiving HEC. METHODS: A decision tree model was constructed to evaluate the cost and health outcomes associated with olanzapine-containing antiemetic regimens and otherwise-identical regimens. One-way sensitivity analyses were conducted to individually investigate the effect of (i) lower complete response (CR) rates of olanzapine, closer to non-olanzapine-containing regimens; (ii) higher FLIE scores for patients who achieved no/incomplete response, closer to FLIE scores of patients achieving a complete response; (iii) differing costs of olanzapine to reflect different costs per hospitals, globally, due to different insurance systems and drug costs; and (iv) varying costs for uncontrolled CINV, to account for varying durations of chemotherapy and accompanying uncontrolled CINV. RESULTS: Olanzapine regimens have an expected cost of $325.24, compared with $551.23 for non-olanzapine regimens. Meanwhile, olanzapine regimens have an expected utility/index of 0.89, relative to 0.87 for non-olanzapine regimens. Olanzapine-containing regimens dominate non-olanzapine-containing regimens even if CR of olanzapine-containing regimens fall to 0.63. Only when CR is between 0.60 and 0.62 is olanzapine both more effective and more costly. CONCLUSION: Olanzapine-containing regimens are both cheaper and more effective in the prophylaxis of CINV in HEC patients, compared with non-olanzapine-containing regimens. Future CINV trial resources should be allocated to understand newer antiemetics and compare them to olanzapine-containing regimens as the control arm. Further analysis should use nationally representative data to examine medication costs by payer type.

Olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting: a systematic review, meta-analysis, cumulative meta-analysis and fragility assessment of the literature.

INTRODUCTION: The aim of this study is to rigorously review the efficacy and safety of olanzapine in defined hematology oncology settings including (1) the setting of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) settings (2) at 5 mg and 10 mg doses, and (3) for response rates for use in the acute, delayed, and overall settings post-MEC and HEC. METHODS: Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched through April 23, 2020. The primary efficacy endpoints were the rate of complete response, in the acute (0-24 h post-chemotherapy), delayed (24-120 h post-chemotherapy), and overall (0-120 h post-chemotherapy) phases. The secondary efficacy endpoints were the rates of no nausea and no emesis, for each phase. Safety endpoints were the rate of no serious adverse events (i.e., no grade 3 or 4 toxicities), as assessed by Common Terminology Criteria for Adverse Events (CTCAE) criteria. The Mantel-Haenszel, random-effects analysis model was used to compute risk ratios and accompanying 95% confidence intervals for each endpoint. For endpoints that statistically favored one arm, absolute risk differences were computed to assess whether there is a 10% or greater difference, used as the threshold for clinical significance by MASCC/ESMO. Fragility indices were also calculated for each statistically significant endpoint, to quantitatively assess the robustness of the summary estimate. A cumulative meta-analysis was conducted for each efficacy meta-analysis with more than 5 studies, also using the Mantel-Haenszel random-effects analysis model. RESULTS: Three studies reported on olanzapine for the rescue of breakthrough chemotherapy-induced nausea and vomiting (CINV); 22 studies reported on olanzapine in the prophylactic setting. For studies reporting on HEC patients, olanzapine-containing regimens were statistically and clinically superior in seven of nine efficacy endpoints in the prophylaxis setting. When olanzapine is administered at a 10-mg dose, it is statistically and clinically superior to control patients in eight of nine endpoints among adults. Olanzapine may be effective in the MEC setting and when administered at 5-mg doses, but the paucity of data leads to notable uncertainty. CONCLUSION: Further RCTs are needed in the setting of MEC patients and administration of olanzapine at a lower 5-mg dose, which may be given to reduce the sedative effect of olanzapine at 10 mg.

Do we know the effects of colorectal cancer screening? A short communication on selective uptake and differential effects of colorectal cancer screening in Scandinavia.

Colorectal cancer (CRC) contributes extensively to the overall cancer burden, with substantial and increasing social inequality in both incidence and survival. In several countries, this social inequality in incidence and survival has been increasing over time, and the increase is expected to continue. To overcome this, it is advised to implement nationwide CRC screening programmes, as these are effective in detecting possible signs of CRC, hence identifying earlier-stage cancer and reducing mortality. However, little is known about the distribution of these effects across population groups. It is possible that the outcomes of CRC screening are not equally distributed among participants, but rather that the screening programme serves some population groups better than others. The aim of this short communication based on published data is to describe the status of selective uptake according to sociodemographic and economic factors in CRC screening in Scandinavia. Furthermore, we raise questions that need to be addressed in future research in order to grasp the full effects of the screening programme and ultimately to ensure high uptake as well as participation in subsequent diagnostic procedures across population groups.

ARAP1 is an independent prognostic biomarker in older women with ovarian high-grade serous adenocarcinoma receiving first-line platinum-based antineoplastic therapy.

Background: Little is known about the biological factors influencing ovarian cancer (OC) patient outcome, especially in older patients who are often underrepresented in clinical trials. We examined alterations in the transcriptomic profile of primary high-grade serous carcinoma (HGSC) samples from older OC patients (>70 years) receiving first-line platinum-based treatment to identify potential biomarkers for prediction of response to this therapy.Material and methods: Tumor samples from 50 HGSC patients were identified from a retrospective cohort, analyzed by gene expression array. The protein expression of selected biomarkers was examined using immunohistochemistry (IHC).Results: Gene expression profiling revealed 81 genes with significantly altered expression in patients experiencing progression after first-line platinum-based treatment within 6 months versus those who progressed later than 12 months. Expression of ankyrin repeat and PH domain 1 (ARAP1) was significantly lower in the group with early versus late progression (p ≤ .01). Correlation between ARAP1 expression and outcome was further confirmed by IHC staining in the discovery cohort (χ2-test, p = .004) and in independent validation cohorts. The sensitivity of ARAP1 allowed identification of 64.7% of patients with early progression in the discovery population, with a specificity of 78.6% and a negative predictive value of 78.6%. Multivariate regression analysis identified ARAP1 as an independent prognostic factor.Conclusions: This hypothesis generating study suggests that low expression of ARAP1 is an independent prognostic biomarker of shorter RFS in older patients with HGSC receiving first-line platinum-based antineoplastic therapy, which could be used to identify patients who should receive more intensive treatment and closer surveillance.

Supportive care in cancer-a MASCC perspective.

The term 'supportive care' arose from the medical oncology literature predominantly in the context of managing the toxicities of cancer treatment but embraces all symptom management through treatment and survivorship. Supportive care should be patient-centred with good communication which includes family and carers and applies across the cancer experience from diagnosis, treatment, survivorship to end of life care. Supportive care encompasses physical and functional, psychological, social and spiritual well-being to improve the quality of life. Supportive care must be evidence-based and thus further research is essential. Supportive care requires screening for some symptoms and tools for patients to report their outcomes. Supportive care has to accommodate new physical toxicities, emotional distress as well as financial toxicity. Supportive care is often delivered by medical oncologists but any organ-related specialist, geriatrician, palliative care clinician, pain specialist, nutritionist, psycho-oncologist, social worker, physiotherapist, nurse or allied health worker who is required to relieve a patient's symptoms or side effects may be involved in a multidisciplinary way. The field is evolving to embrace technology such as eHealth and mHealth capabilities which will enhance integrated care.

Patient self-testing of white blood cell count and differentiation: A study of feasibility and measurement performance in a population of Danish cancer patients.

OBJECTIVE: Patients in anticancer treatment with a known side effect of neutropenia are monitored closely with laboratory measurements of white blood cell count (WBC) and differentiation. This study sought to evaluate measurement properties and feasibility of patients' self-testing using a point-of-care testing (POCT) device. METHODS: A prospective feasibility and measurement study comparing the standard measurement of cancer patients' WBC and neutrophil count with POCT measurements. The study included 60 outpatients and 22 inpatients from a department of oncology at a university hospital. RESULTS: Patients successfully conducted 106 measurements using the POCT device. 46% of the patients were >70 years. Weighted Deming regression analysis showed minimal yet significant proportional bias between methods, with POCT increasingly underestimating both total WBC and neutrophils compared with the standard method the higher the count. Over 90% of patients reported they were willing and considered themselves able to use the POCT device at home. CONCLUSIONS: The instrument can be used for self-testing of post-anticancer leukopenia and has sufficient measurement precision for patient risk stratification. Patients are able and willing to conduct measurements including when in a situation of acute illness. Further studies are needed to confirm safety and value within patients' own home.

Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer.

BACKGROUND: Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer. METHODS: In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2:1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival. RESULTS: Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval [CI], 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; P<0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications. CONCLUSIONS: Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274 .).

Efficacy and safety of immune checkpoint inhibitors in a Danish real life non-small cell lung cancer population: a retrospective cohort study.

Background: To investigate effect and toxicity of immune checkpoint inhibition (ICI) in a Danish real-life non-small cell lung cancer (NSCLC) population. By including patients underrepresented in clinical trials, such as those with brain metastasis (BM), higher age, more comorbidity and poorer performance status (ECOG), comparison of unselected patients to clinical trial populations is possible. Material and methods: Real life data were gathered from 118 consecutive NSCLC patients with incurable NSCLC treated with ICI at the Department of Oncology at the University Hospital of Odense, Denmark from September 2015 to April 2018. Immune-related adverse events (irAEs) grades 3-5 were registered prospectively during the same period. Additional patient related data were obtained retrospectively from patients' files. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier estimates, the log-rank test and cox regression analysis performed for factors affecting survival. Results: Median age for patients was 66 years (IQR 59-71) and 62 years (range: 55-64) for those with BM. Females 63%; adenocarcinoma (AC)/squamous/others 69%/23%/8%; ECOG ≥ 2 10%; bone/brain/liver metastases 36%/18%/15%; PD-L1 (TPS) <1%/ ≥ 1%/ ≤ 49%/ ≥ 50%/NR: 3%/14%/68%/15%; baseline autoimmunity 10%, Charlson's Comorbidity Index Score (CCIS) ≥ 2 39%, treatment line: 1st/2nd/ ≥ 3rd 39%/30%/31%. Median OS for patients receiving ICI in ≥2 line was 11.5 months versus not reached in first line (HR 2.6, [95% CI: 1.3-5.0], p = .005). For patients with BM, the median OS was 8.2 months (HR 1.38, [95% CI: 0.7-2.5], p = .37). Twenty-four percent of patients terminated ICI due to irAE grades 3-5 alone (grade 5, n = 1), which were not associated with higher age or BM. Conclusions: OS and PFS were comparable to clinical trial reports. Long-lasting remission is also possible in patients with BM. Real-life populations have higher rates of irAE grades 3 and 4 than reported in clinical trials, but it does not seem to impact median OS.

Nausea in advanced cancer: relationships between intensity, burden, and the need for help.

PURPOSE: This study aimed at expanding the knowledge of nausea in patients with advanced cancer by elucidating (a) the prevalences of patients having nausea, experiencing nausea as a problem, and having a need for help with their nausea, respectively, (b) determining variables associated with nausea, and (c) investigating the relation between nausea and the need for help regarding nausea. METHODS: In 2004-2006, the EORTC QLQ-C30 and the Three-Levels-of-Needs Questionnaire (3LNQ) were mailed to 2364 patients with advanced cancer who had been in contact with one of the 54 hospital departments within the past year. Further information was collected from medical records. RESULTS: Patient-response rate was 61%. Twenty-two percent reported having had some degree of nausea within the past week, with a mean nausea score of 10.4 and a two-item combined nausea and vomiting score of 7.5 (0-100, 100 = "very much"). Factors associated with nausea on the multivariate level were contact type (inpatient/outpatient) and treatment status (receiving ongoing oncologic treatment yes/no). "Nausea intensity" and "nausea problem burden" showed acceptable abilities to distinguish between patients having or not having an unmet need for help regarding nausea with areas under the curve (AUCs) of 0.81 and 0.82, respectively. CONCLUSIONS: Around one in four patients with advanced cancer reported nausea within the past week, highest in patients who were inpatients or undergoing active oncologic treatment. Almost all patients reporting nausea on the EORTC QLQ-C30 experienced this to be a problem, and the 3LNQ can therefore be restricted to cases where additional details are needed.